Cisplatin nephrotoxicity is not detected by urinary cell-cycle arrest biomarkers in lung cancer patients

Toprak, Zeki; Cebeci, Egemen; Helvaci, Serife Aysen; Toprak, İlkim Deniz; Kutlu, Yasin; Sakin, Abdullah; Tükek, Tufan

doi:10.1007/s11255-017-1556-4

Cited by 11 publications

(7 citation statements)

References 20 publications

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“…In one clinical study, 4 of 32 patients receiving cisplatin developed AKI, and the AUC-ROC value for TIMP2ÂIGFBP7 was 0.92 within 72 h. 73 However, another study that measured the two biomarkers individually found that there was no change in IGFBP7 concentrations 24 h after cisplatin administration, whereas a 1.1-fold increase in TIMP2 levels could be observed. 71 While 13 patients developed AKI in this study, the AUC-ROC value for the product of TIMP2ÂIGFBP7 was only 0.46 at 24 h. A third study of 46 patients also showed no significant changes from baseline for either TIMP2 or IGFBP7 as well as for TIMP2ÂIGFBP7 at days 3 and 10 after cisplatin treatment. 72 However, additional studies are required to further validate this test in cisplatin-treated patients and to find the optimal time-points for clinical use in ambulatory patients at risk of AKI.…”

Section: Calbindinmentioning

confidence: 50%

Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy

George

Joy²,

Aleksunes

2017

Exp Biol Med (Maywood)

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Despite recent progress in the development of novel approaches to treat cancer, traditional antineoplastic drugs, such as cisplatin, remain a mainstay of regimens targeting solid tumors. Use of cisplatin is limited by acute kidney injury, which occurs in approximately 30% of patients. Current clinical measures, such as serum creatinine and estimated glomerular filtration rate, are inadequate in their ability to detect acute kidney injury, particularly when there is only a moderate degree of injury. Thus, there is an urgent need for improved diagnostic biomarkers to predict nephrotoxicity. There is also interest by the U.S. Food and Drug Administration to validate and implement new biomarkers to identify clinical and subclinical acute kidney injury in patients during the drug approval process. This minireview provides an overview of the current literature regarding the utility of urinary proteins (albumin, beta-2-microglobulin, N-acetyl-D-glucosaminidase, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and cystatin C) as biomarkers for cisplatin-induced AKI. Many of the well-studied urinary proteins (KIM-1, NGAL, B2M, albumin) as well as emerging biomarkers (calbindin, monocyte chemotactic protein-1, and trefoil factor 3) display distinct patterns of time-dependent excretion after cisplatin administration. Implementation of these biomarker proteins in the oncology clinic has been hampered by a lack of validation studies. To address these issues, large head-to-head studies are needed to fully characterize time-dependent responses and establish accurate cutoff values and ranges, particularly in cancer patients. Impact statement There is growing interest in using urinary protein biomarkers to detect acute kidney injury in oncology patients prescribed the nephrotoxic anticancer drug cisplatin. We aim to synthesize and organize the existing literature on biomarkers examined clinically in patients receiving cisplatin-containing chemotherapy regimens. This minireview highlights several proteins (kidney injury molecule-1, beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, calbindin, monocyte chemotactic protein-1, trefoil factor 3) with the greatest promise for detecting cisplatin-induced acute kidney injury in humans. A comprehensive review of the existing literature may aid in the design of larger studies needed to implement the clinical use of these urinary proteins as biomarkers of kidney injury.

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Section: Calbindinmentioning

confidence: 50%

Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy

George

Joy²,

Aleksunes

2017

Exp Biol Med (Maywood)

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“…Cisplatin-associated AKI was detected in 13 patients (28%) out of 45 enrolled. 141 There was no difference between creatinine, IGFBP7 and (IGFBP7 × TIMP2)/1000 (the at risk score) levels before and after treatment with cisplatin. However, in another study, urinary [TIMP2] x [IGFBP7] was found to be a useful tool for early identification of patients who are at risk for cisplatin-induced AKI.…”

Section: Timp2 and Igfbp7mentioning

confidence: 82%

Biomarkers of Drug-Induced Kidney Toxicity

Griffin

Faubel²,

Edelstein³

2019

Therapeutic Drug Monitoring

168

105

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Blood urea nitrogen (BUN) and serum creatinine are imperfect markers of kidney function because they are influenced by many renal and non-renal factors independent of kidney function. A biomarker that is released directly into the blood or urine by the kidney in response to injury may be a better early marker of drug-induced kidney toxicity than BUN and serum creatinine. Urine albumin and urine protein, as well as urinary markers kidney injury molecule-1 (KIM-1), β2-microglobulin (B2M), cystatin C, clusterin, and trefoil factor-3 (TFF-3) have been accepted by the Food and Drug Administration (FDA) and European Medicines Agency as highly sensitive and specific urinary biomarkers to monitor drug-induced kidney injury in preclinical studies and on a case-by-case basis in clinical trials. Other biomarkers of drug-induced kidney toxicity that have been detected in the urine of rodents or patients include IL-18 (interleukin-18), NGAL (neutrophil gelatinase-associated lipocalin), Netrin-1, liver type fatty acid binding protein (L-FABP), urinary exosomes, and TIMP2 (insulin-like growth factor-binding protein 7)/IGFBP7 (insulin-like growth factor binding protein 7), also known as NephroCheck®, the first FDA-approved biomarker testing platform to detect acute kidney injury (AKI) in patients. In the future, a combined use of functional and damage markers may advance the field of biomarkers of drug kidney toxicity. Earlier detection of drug-induced kidney toxicity with a kidney specific biomarker may result in the avoidance of nephrotoxic agents in clinical studies and may allow for earlier intervention to repair damaged kidneys.

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“…] levels after platinum administration discriminated for the risk of AKI with an area under curve of 0.92, sensitivity was 50%, specificity was 87%, negative predictive value was 95% and positive predictive value was 25% for the prediction of AKI within 72 hours. In contrast, Toprak et al49 observed 45 patients with lung cancer treated with cisplatin: AKI prevalence was 28% in this group of patients. There was no difference between creatinine and [TIMP-2] × [IGFBP-7] levels before and after treatment.…”

mentioning

confidence: 79%

<p>Evaluating Nephrocheck<sup>®</sup> as a Predictive Tool for Acute Kidney Injury</p>

Nalesso¹,

Cattarin²,

Gobbi³

et al. 2020

IJNRD

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Acute kidney injury (AKI) is a common complication in critically ill patients in the intensive settings with increased risks of short-and long-term complications and mortality. AKI is also associated with an increased length of stay in intensive care units (ICU) and worse kidney function recovery at hospital discharge. The management of AKI is one of the major challenges for nephrologists and intensivists overall for its early diagnosis. The current KDIGO criteria used to define AKI include the serum creatinine and urinary output that are neither sensitive nor specific markers of kidney function, since they can be altered only after hours from the kidney injury. In order to allow an early AKI detection, in the last years, several studies focused on the identification of new biomarkers. Among all these markers, urinary insulin-like growth factor-binding protein (IGFBP-7) and tissue inhibitor of metalloproteinase (TIMP-2) have been proven as the best-performing and have been proposed as a predictive tool for the AKI detection in the critical settings in order to perform an early diagnosis. Patients undergoing major surgery, cardiac surgery, those with hemodynamic instability or those with sepsis are believed to be the top priority patient populations for the biomarker test. In this view, the urinary [TIMP-2] x [IGFBP-7] becomes an important tool for the early detection of patients at high risk for AKI and its integration with the local ICU experience has to provide a multidisciplinary management of AKI with the institution of a rapid response team in order to assess patients and customize AKI management.

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Cisplatin nephrotoxicity is not detected by urinary cell-cycle arrest biomarkers in lung cancer patients

Abstract: Although urinary IGFBP7 and TIMP-2 levels are used as biomarkers for early detection of AKI for patients in intensive care units and after surgery, they seem not to be useful for early detection of AKI due to cisplatin.

Cited by 11 publications

References 20 publications

Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy

Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy

Biomarkers of Drug-Induced Kidney Toxicity

<p>Evaluating Nephrocheck<sup>®</sup> as a Predictive Tool for Acute Kidney Injury</p>

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